دورية أكاديمية
The role of non-genomic actions of progesterone and its membrane receptor agonist in ovarian cancer cell death.
| العنوان: | The role of non-genomic actions of progesterone and its membrane receptor agonist in ovarian cancer cell death. |
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| المؤلفون: | Koyanagi T; Department of Obstetrics and Gynecology, School of Medicine, Jichi Medical University, Tochigi, Japan., Saga Y; Department of Obstetrics and Gynecology, School of Medicine, Jichi Medical University, Tochigi, Japan.; Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan., Takahashi Y; Department of Obstetrics and Gynecology, School of Medicine, Jichi Medical University, Tochigi, Japan., Tamura K; Department of Obstetrics and Gynecology, School of Medicine, Jichi Medical University, Tochigi, Japan., Yoshiba T; Department of Obstetrics and Gynecology, School of Medicine, Jichi Medical University, Tochigi, Japan., Takahashi S; Department of Obstetrics and Gynecology, School of Medicine, Jichi Medical University, Tochigi, Japan., Taneichi A; Department of Obstetrics and Gynecology, School of Medicine, Jichi Medical University, Tochigi, Japan., Takei Y; Department of Obstetrics and Gynecology, School of Medicine, Jichi Medical University, Tochigi, Japan., Mizukami H; Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan., Fujiwara H; Department of Obstetrics and Gynecology, School of Medicine, Jichi Medical University, Tochigi, Japan. |
| المصدر: | Cancer reports (Hoboken, N.J.) [Cancer Rep (Hoboken)] 2024 Jan; Vol. 7 (1), pp. e1934. Date of Electronic Publication: 2023 Nov 27. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: John Wiley & Sons, Inc Country of Publication: United States NLM ID: 101747728 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2573-8348 (Electronic) Linking ISSN: 25738348 NLM ISO Abbreviation: Cancer Rep (Hoboken) Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Hoboken, NJ : John Wiley & Sons, Inc., [2018]- |
| مواضيع طبية MeSH: | Progesterone*/pharmacology , Progesterone*/physiology , Ovarian Neoplasms*/drug therapy, Female ; Humans ; Receptors, Progesterone/genetics ; Receptors, Progesterone/metabolism ; bcl-2-Associated X Protein ; Progestins/pharmacology ; Medroxyprogesterone Acetate/pharmacology ; Genomics ; Cell Death |
| مستخلص: | Background: Progesterone therapy is a relatively inexpensive treatment option for endometrial and breast cancers, with few side effects. Two signaling pathways usually mediate the physiological effects of progesterone, namely genomic and non-genomic actions. Genomic action occurs slowly via the nuclear progesterone receptor (PR), whereas the membrane progesterone receptor (mPR) induces rapid non-genomic action. Aims: We investigated the effects of progesterone and various PR agonists on ovarian cancer cells. Methods and Results: PR expression of six serous ovarian cancer cell lines was examined by western blotting, and mPR expression was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). PR-negative and mPR-positive ovarian cancer cells were exposed to progesterone and seven types of PR agonists (medroxyprogesterone acetate [MPA], dehydroepiandrosterone, dienogest, levonorgestrel, drospirenone, pregnenolone, and allopregnanolone) at 10-400 μM, and viable cell counts after exposure for 30 min were measured using the water-soluble tetrazolium (WST-1) assay. Ovarian cancer cell lines were exposed to 100 μM progesterone, and the expression of BAX, a pro-apoptotic protein, after 1-5 min was examined by western blotting. Western blotting detected no PR expression in the six serous ovarian cancer cell lines. In contrast, RT-qPCR detected mPR expression in all six serous ovarian cancer cell lines. Progesterone and MPA-induced cell death in all tested ovarian cancer cell lines in a concentration-dependent manner, whereas no effect was observed for other PR agonists. Western blotting revealed that pro-apoptotic protein BAX expression occurred 1 min after exposure to progesterone, suggesting that the cytocidal effects are mediated by rapid non-genomic action. Conclusion: Progesterone and MPA exhibited a rapid cytocidal effect on PR-negative ovarian cancer cells through non-genomic action. Progesterone and MPA could be novel adjuvant therapies for ovarian cancer. (© 2023 The Authors. Cancer Reports published by Wiley Periodicals LLC.) |
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| معلومات مُعتمدة: | 17K11294 Ministry of Education, Culture, Sports, Science and Technology; 19K18702 Ministry of Education, Culture, Sports, Science and Technology; 20K09627 Ministry of Education, Culture, Sports, Science and Technology; 22K09551 Ministry of Education, Culture, Sports, Science and Technology |
| فهرسة مساهمة: | Keywords: cell death; genomics; medroxyprogesterone acetate; ovarian cancer; progesterone; progesterone receptor |
| المشرفين على المادة: | 4G7DS2Q64Y (Progesterone) 0 (Receptors, Progesterone) 0 (bcl-2-Associated X Protein) 0 (Progestins) C2QI4IOI2G (Medroxyprogesterone Acetate) |
| تواريخ الأحداث: | Date Created: 20231128 Date Completed: 20240129 Latest Revision: 20240314 |
| رمز التحديث: | 20240314 |
| مُعرف محوري في PubMed: | PMC10809274 |
| DOI: | 10.1002/cnr2.1934 |
| PMID: | 38013666 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2573-8348 |
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| DOI: | 10.1002/cnr2.1934 |